The high incidence of fungal pathogens has become a global issue for crop protection. A promising strategy to control fungal plant infections is based on the use of nature-inspired compounds. The ...cytochrome bc1 complex is an essential component of the cellular respiratory chain and is one of the most important fungicidal targets. Natural products have played a crucial role in the discovery of cytochrome bc1 inhibitors, as proven by the development of strobilurins, one of the most important classes of crop-protection agents, over the past two decades. In this review, we summarize advances in the exploration of natural product scaffolds for the design and development of new bc1 complex inhibitors. Particular emphasis is given to molecular modeling-based approaches and structure-activity relationship (SAR) studies performed to improve the stability and increase the potency of natural precursors. The collected results highlight the versatility of natural compounds and provide an insight into the potential development of nature-inspired derivatives as antifungal agents.
Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the ...cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.
•MEP facilitation following intermittent theta-burst stimulation (iTBS) is associated with specific iTBS-evoked EEG oscillations.•Baseline MEP amplitude and iTBS-evoked beta oscillations predict iTBS ...aftereffects.•Our TMS-EEG study identified cortical mechanisms underlying iTBS variability that are potentially clinically relevant.
To test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).
In a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.
The facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.
The results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.
These observations can be used to optimize iTBS investigational and therapeutic applications.
Salivary caffeine in Parkinson's disease Leodori, Giorgio; De Bartolo, Maria Ilenia; Belvisi, Daniele ...
Scientific reports,
05/2021, Letnik:
11, Številka:
1
Journal Article
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We aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson's disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 ...PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.
Abstract Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, ...such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.
Introduction. The Geriatric Depression Scale (GDS) is commonly used to assess depressive symptoms, but its psychometric properties have never been examined in Italian people with Parkinson’s disease ...(PD). The aim of this study was to study the reliability and validity of the Italian version of the GDS in a sample of PD patients. Methods. The GDS was administered to 74 patients with PD in order to study its internal consistency, test-retest reliability, construct, and discriminant validity. Results. The internal consistency of GDS was excellent (α = 0.903), as well as the test-retest reliability (ICC = 0.941 95% CI: 0.886–0.970). GDS showed a strong correlation with instruments related to the depression (ρ = 0.880) in PD (ρ = 0.712) and a weak correlation with generic measurement instruments (−0.320 < ρ <−0.217). An area under the curve of 0.892 (95% CI 0.809–0.975) indicated a moderate capability to discriminate depressed patients to nondepressed patient, with a cutoff value between 15 and 16 points that predicts depression (sensitivity = 87%; specificity = 82%). Conclusion. The GDS is a reliable and valid tool in a sample of Italian PD subjects; this scale can be used in clinical and research contexts.
In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe ...networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkinsonism. With the technique of transcranial magnetic stimulation, we investigated long-term potentiation– and long-term depression–like plasticity in the primary motor cortex of bv-FTD and nfv-PPA patients, with and without parkinsonism, by using the theta-burst stimulation (TBS) protocol. We applied the intermittent TBS and continuous TBS in 20 FTD patients and 18 age-matched healthy subjects. Results were also compared with those achieved in a cohort of age-matched patients with Parkinson's disease. The responses to TBS were abnormal in FTD patients with parkinsonism. By contrast, the TBS induced normal responses in patients with both nfv-PPA and bv-FTD without parkinsonism. Finally, responses to TBS were comparable in patients with FTD with parkinsonism and patients with Parkinson's disease. We provide evidence of abnormal primary motor cortex long-term potentiation–/long-term depression–like plasticity in patients with FTD and parkinsonism suggesting neurodegenerative processes in the corticobasal ganglia-thalamo-cortical motor networks in these patients.
Postural instability (PI) in Parkinson’s disease (PD) exposes patients to an increased risk of falls (RF). While dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in ...advanced PD patients, their effects on PI and RF remain elusive. PI and RF were assessed using a stabilometric platform in six advanced PD patients. Patients were evaluated in OFF and ON dopaminergic medication and under four DBS settings: with DBS off, DBS bilateral, and unilateral DBS of the more- or less-affected side. Our findings indicate that dopaminergic medication by itself exacerbated PI and RF, and DBS alone led to a decline in RF. No combination of medication and DBS yielded a superior improvement in postural control compared to the baseline combination of OFF medication and the DBS-off condition. Yet, for ON medication, DBS significantly improved both PI and RF. Among DBS conditions, DBS bilateral provided the most favorable outcomes, improving PI and RF in the ON medication state and presenting the smallest setbacks in the OFF state. Conversely, the more-affected side DBS was less beneficial. These preliminary results could inform therapeutic strategies for advanced PD patients experiencing postural disorders.
In healthy subjects (HS), transcranial magnetic stimulation (TMS) demonstrated an increase in motor-evoked potential (MEP) amplitudes during specific linguistic tasks. This finding indicates ...functional connections between speech-related cortical areas and the dominant primary motor cortex (M1).
To investigate M1 function with TMS and the speech-related cortical network with neuroimaging measures in frontotemporal dementia (FTD), including the non-fluent variant of primary progressive aphasia (nfv-PPA) and the behavioral variant of FTD (bv-FTD).
M1 excitability changes during specific linguistc tasks were examined using TMS in 24 patients (15 with nfv-PPA and 9 with bv-FTD) and in 18 age-matched HS. In the same patients neuroimaging was used to assess changes in specific white matter (WM) bundles and grey matter (GM) regions involved in language processing, with diffusion tensor imaging (DTI) and voxel-based morphometry (VBM).
During the linguistic task, M1 excitability increased in HS, whereas in FTD patients it did not. M1 excitability changes were comparable in nfv-PPA and bv-FTD. DTI revealed decreased fractional anisotropy in the superior and inferior longitudinal and uncinate fasciculi. Moreover, VBM disclosed GM volume loss in the left frontal operculum though not in the parietal operculum or precentral gyrus. Furthermore, WM and GM changes were comparable in nfv-PPA and bv-FTD. There was no correlation between neurophysiological and neuroimaging changes in FTD. Atrophy in the left frontal operculum correlated with linguistic dysfunction, assessed by semantic and phonemic fluency tests.
We provide converging neurophysiological and neuroimaging evidence of abnormal speech-related cortical network activation in FTD.
•M1 excitability during linguistic tasks increased in HS but not in FTD patients.•DTI revealed reduced FA in SLF-t, ILF and UnF in FTD patients.•Left frontal operculum atrophy correlated with linguistic dysfunction in FTD.•Neurophysiological and neuroimaging findings were comparable in nfv-PPA and bv-FTD.•FTD patients display altered speech-related cortical network activation.
Patients with frontotemporal degeneration (FTD) often manifest parkinsonism, which likely results from cortical and subcortical degeneration of brain structures involved in motor control. We used a ...multimodal magnetic resonance imaging (MRI) approach to investigate possible structural and/or functional alterations in FTD patients with and without parkinsonism (Park+ and Park-).
Thirty FTD patients (12 Park+, 18 Park-) and 30 healthy controls were enrolled and underwent 3T MRI scanning. MRI analyses included: (1) surface-based morphometry; (2) basal ganglia and thalamic volumetry; (3) diffusion-based probabilistic tractography of fiber tracts connecting the supplementary motor area (SMA) and primary motor cortex (M1) to the putamen, globus pallidus, and thalamus; and (4) resting-state functional connectivity (RSFC) between the aforementioned regions.
Patients in Park+ and Park- groups showed comparable patterns of cortical thinning in frontotemporal regions and reduced thalamic volume with respect to controls. Only Park+ patients showed reduced putaminal volume and reduced fractional anisotropy of the fibers connecting the SMA to the globus pallidus, putamen, and thalamus, with respect to controls. Park+ patients also showed decreased RSFC between the SMA and putamen with respect to both Park- patients and controls.
The present findings support the hypothesis that FTD patients with parkinsonism are characterized by neurodegenerative processes in specific corticobasal ganglia-thalamocortical motor loops.
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